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This update is devoted to discussion of optimal supportive and palliative care of patients with pancreatic cancer. Approximately 33,000 new cases of pancreatic cancer are predicted for the U.S. in 2002. Because diagnosis and intervention occur late in the course of this disease, the vast majority of patients already have metastatic disease at the time of diagnosis. These tumors are relatively resistant to systemic chemotherapy, making pancreatic cancer the fourth leading cause of cancer‐related death in the U.S. and the Western world. For these reasons, efforts at identifying and treating disease‐related symptomatology are priorities. This update overviews symptom management, supportive care strategies, and both standard and emerging palliative chemotherapy options. The incorporation of molecularly targeted therapies into treatment of metastatic pancreatic cancer is reviewed as well. These strategies are of relevance to internists, gastroenterologists, oncologists, and other specialists who care for patients with pancreatic cancer.

Background. Single agents have only modest activity as treatment for metastatic pancreatic cancer with response rates of less than 10% and median survivals of less than 6 months. Evaluations of single‐agent gemcitabine and rubitecan as second‐line treatment for relapsed pancreatic cancer have reported good patient tolerability and median survivals of 3.85 months and 4.7 months, respectively. Regimens incorporating two drugs have demonstrated encouraging activity and clinical impact compared with single‐agent therapy. G‐FLIP is a regimen designed to incorporate four active single agents into a tolerable and active combination. This analysis is a retrospective evaluation of the efficacy and safety of the G‐FLIP regimen as second‐line chemotherapy in a series of consecutively treated patients with metastatic pancreatic cancer. Methods. G‐FLIP was administered over 48 hours and repeated every 2 weeks. Day 1 treatment consisted of sequentially administered gemcitabine 500 mg/m2, irinotecan 80 mg/m2, leucovorin 300 mg, 5‐fluorouracil (5‐FU) 400 mg/m2bolus followed by infusional 5‐FU 600 mg/m2over 8 hours. Day 2 treatment consisted of leucovorin 300 mg and 5‐FU 400 mg/m2bolus, followed by cisplatin 50 to 75 mg/m2, and then infusional 5‐FU 600 mg/m2over 8 hours. Results. Thirty‐four patients with histologically confirmed metastatic pancreatic cancer were consecutively treated. The median patient age was 64.5 years (range 41‐82 years) and all patients had objective disease progression on prior therapy: 32 patients had disease progression with gemcitabine and 31 had disease progression with a gemcitabine/5‐fluorouracil/cisplatin combination. Grade 3‐4 hematological toxicities included anemia (23%), thrombocytopenia (53%), and neutropenia (38%). There were no grade 3‐4 neutropenic fevers, treatment‐related mortalities, or withdrawals. Nonhematological grade 3‐4 toxicities were rare: nausea/vomiting (3%), neurotoxicity (3%), nephrotoxicity (6%), and diarrhea (3%). Based on RECIST criteria a partial response (PR) was attained in eight patients (24%) and seven patients had stable disease (SD). Seven and six patients who attained a PR or SD, respectively, had disease progression with prior gemcitabine‐based therapy. The median time to disease progression for all 34 patients was 3.9 months and 5.9 months for the eight patients who attained a PR. Median overall survival for all 34 patients was 10.3 months. Conclusion. Adding a single new drug such as irinotecan to the same first‐line chemotherapy combination upon disease progression may be an important alternative to switching to different drug classes for treatment of relapsed/resistant cancer. The promising clinical outcomes and moderate toxicity associated with G‐FLIP in this heavily pretreated group warrant development of this novel regimen including tests as first‐line therapy in patients with diseases likely to be responsive to the drugs contained in this combination.